The University of Tokyo · Medicine
Professor Yasuyuki Goto's research lab focuses on parasitic diseases, particularly leishmaniasis and Chagas' disease, with an emphasis on identifying protective antigens and understanding host-parasite interactions. The lab employs bioinformatic and immunological approaches to discover tandem repeat (TR) domain-containing proteins as potential vaccine candidates and serodiagnostic markers. They also investigate host genetic factors, such as SNPs in human genes like PTPN11 (SHP-2) and EGF, that influence susceptibility to gastric atrophy and cancer in the context of chronic infections like *H. pylori*. The lab integrates parasitology, immunology, and molecular genetics to develop novel diagnostics and vaccines for neglected tropical diseases and infection-associated cancers.
Figures are computed from collected data and may differ slightly.
A subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, a multiple-antigen vaccine will likely be essential. However, the cost of a vaccine to be used in developing countries must be considered. We describe herein a multiantigen vaccine candidate comprised of antigens known to be protective in animal models, including dogs, and to be recognized by humans immune to
Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, often acting as targets of B-cell responses. However, the extent of the repeats within Trypanosoma cruzi, the causative agent of Chagas' disease, has not been examined well. Here, we present a systematic survey of the TR genes found in T. cruzi, in comparison with other organisms. Although the characteristics of TR genes varied from organism to organism, the presence of genes having large TR domains was uniq
Helicobacter pylori (H. pylori) plays a crucial role in the development of gastric atrophy and cancer, and cagA-positive strains, which are universal in Japan, increase the risk of these outcomes substantially. The CagA protein is injected from attached H. pylori into gastric epithelial cells and undergoes Src-dependent tyrosine phosphorylation and activation of the eukaryotic phosphatase SHP-2. The CagA/SHP-2 interactions elicit cellular changes that increase the risk of carcinogenesis. We inve
With large amounts of parasite gene sequence available, additional bioinformatic tools to screen these sequences for identifying genes encoding antigens are needed. Proteins containing tandem repeat (TR) domains are often B-cell antigens, and antibody responses toward TR domains of the proteins are dominant in human infected with certain parasites. We hypothesized that antigens of serological significance could be identified with a search for TR domains. Here we show the result of bioinformatic
The etiology of gastric cancer is not well-understood. Epidermal growth factor (EGF) transduces growth signals to mitogen-activated protein kinase via RAS and BRAF, and EGF/EGF receptor interaction is important for tumor growth and progression. Previous studies have reported that the EGF +61 (A/G) single nucleotide polymorphism in the 5'-untranslated region of the EGF gene is functional, and is associated with gastric cancer and various malignancy. Individuals with the EGF A/A genotype produce l
Visceral leishmaniasis (VL) is a form of leishmaniasis, which is caused by infection with the protozoan parasite Leishmania, and is often fatal unless it is treated. Rapid and accurate diagnosis of VL is important for effective treatment. Here we report the cloning of previously undescribed tandem repeat (TR) proteins of Leishmania infantum and an evaluation of VL patient antibody responses to the corresponding proteins. By screening an L. infantum expression library with sera from human VL pati
Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, and they are often targets of B-cell responses. Through systematic analyses of whole proteomes, we recently demonstrated that two trypanosomatid parasites, Leishmania infantum and Trypanosoma cruzi, are rich in antigenic proteins with large TR domains. However, the reason that these proteins are antigenic was unclear. Here, by performing molecular, immunological, and bioinformatic characterizations of Leishm
Hemophagocytosis is a phenomenon in which macrophages phagocytose blood cells. There are reports on up-regulated hemophagocytosis in patients with infectious diseases including typhoid fever, tuberculosis, influenza and visceral leishmaniasis (VL). However, mechanisms of infection-associated hemophagocytosis remained elusive due to a lack of appropriate animal models. Here, we have established a mouse model of VL with hemophagocytosis. At 24 weeks after infection with 1 x 10(7) Leishmania donova
Over 55 million people reportedly suffer from dementia worldwide. In Japan, it is estimated that 1 in 5 people over 65 years old will have dementia by 2025, of which more than 20% will live with symptoms that require home/nursing care. Given the lack of effective medical treatments for dementia, informal caregivers play essential roles in allowing dementia patients to live with dignity. Our review focusing on caregiver burden showed that this burden has not been sufficiently addressed, despite h
Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphi
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